Scopolamine in Bipolar Depression

Summary

This is a single-site, randomised, double-blind, placebo-controlled, parallel, phase IIb clinical trial. The primary objective of the SCOPE-BD study is to investigate the efficacy and safety of IV Scopolamine, compared to placebo, in reducing severity of depression in individuals with bipolar disorder who are experiencing a depressive episode of at least moderate severity

Timeline

Start

2021-03-23

Primary completion

2024-02-22

Completion

2024-02-22

Publications

• Background Belmaker RH. Bipolar disorder. N Engl J Med. 2004 Jul 29;351(5):476-86. doi: 10.1056/NEJMra035354. No abstract available.
• Background Bonner TI, Buckley NJ, Young AC, Brann MR. Identification of a family of muscarinic acetylcholine receptor genes. Science. 1987 Jul 31;237(4814):527-32. doi: 10.1126/science.3037705.
• Background Cannon DM, Carson RE, Nugent AC, Eckelman WC, Kiesewetter DO, Williams J, Rollis D, Drevets M, Gandhi S, Solorio G, Drevets WC. Reduced muscarinic type 2 receptor binding in subjects with bipolar disorder. Arch Gen Psychiatry. 2006 Jul;63(7):741-7. doi: 10.1001/archpsyc.63.7.741.
• Background Cannon DM, Klaver JK, Gandhi SK, Solorio G, Peck SA, Erickson K, Akula N, Savitz J, Eckelman WC, Furey ML, Sahakian BJ, McMahon FJ, Drevets WC. Genetic variation in cholinergic muscarinic-2 receptor gene modulates M2 receptor binding in vivo and accounts for reduced binding in bipolar disorder. Mol Psychiatry. 2011 Apr;16(4):407-18. doi: 10.1038/mp.2010.24. Epub 2010 Mar 30.
• Background Davis CE, Applegate WB, Gordon DJ, Curtis RC, McCormick M. An empirical evaluation of the placebo run-in. Control Clin Trials. 1995 Feb;16(1):41-50. doi: 10.1016/0197-2456(94)00027-z.
• Background Davis KL, Berger PA, Hollister LE, Defraites E. Physostigmine in mania. Arch Gen Psychiatry. 1978 Jan;35(1):119-22. doi: 10.1001/archpsyc.1978.01770250121012.
• Background Drevets WC, Furey ML. Replication of scopolamine's antidepressant efficacy in major depressive disorder: a randomized, placebo-controlled clinical trial. Biol Psychiatry. 2010 Mar 1;67(5):432-8. doi: 10.1016/j.biopsych.2009.11.021. Epub 2010 Jan 15.
• Background Dwyer JM, Lepack AE, Duman RS. mTOR activation is required for the antidepressant effects of mGluR(2)/(3) blockade. Int J Neuropsychopharmacol. 2012 May;15(4):429-34. doi: 10.1017/S1461145711001702. Epub 2011 Nov 24.
• Background Ellis JS, Zarate CA Jr, Luckenbaugh DA, Furey ML. Antidepressant treatment history as a predictor of response to scopolamine: clinical implications. J Affect Disord. 2014 Jun;162:39-42. doi: 10.1016/j.jad.2014.03.010. Epub 2014 Mar 26.
• Background Ferrari AJ, Stockings E, Khoo JP, Erskine HE, Degenhardt L, Vos T, Whiteford HA. The prevalence and burden of bipolar disorder: findings from the Global Burden of Disease Study 2013. Bipolar Disord. 2016 Aug;18(5):440-50. doi: 10.1111/bdi.12423.
• Background Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, Fawcett J. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010 Jan 6;303(1):47-53. doi: 10.1001/jama.2009.1943.
• Background Furey ML, Drevets WC. Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Arch Gen Psychiatry. 2006 Oct;63(10):1121-9. doi: 10.1001/archpsyc.63.10.1121.
• Background Furey ML, Nugent AC, Speer AM, Luckenbaugh DA, Hoffman EM, Frankel E, Drevets WC, Zarate CA Jr. Baseline mood-state measures as predictors of antidepressant response to scopolamine. Psychiatry Res. 2012 Mar 30;196(1):62-7. doi: 10.1016/j.psychres.2012.01.003. Epub 2012 Feb 18.
• Background Furey ML, Drevets WC, Hoffman EM, Frankel E, Speer AM, Zarate CA Jr. Potential of pretreatment neural activity in the visual cortex during emotional processing to predict treatment response to scopolamine in major depressive disorder. JAMA Psychiatry. 2013 Mar;70(3):280-90. doi: 10.1001/2013.jamapsychiatry.60.
• Background GERSHON S, SHAW FH. Psychiatric sequelae of chronic exposure to organophosphorus insecticides. Lancet. 1961 Jun 24;1(7191):1371-4. doi: 10.1016/s0140-6736(61)92004-9. No abstract available.
• Background Gillin JC, Sutton L, Ruiz C, Darko D, Golshan S, Risch SC, Janowsky D. The effects of scopolamine on sleep and mood in depressed patients with a history of alcoholism and a normal comparison group. Biol Psychiatry. 1991 Jul 15;30(2):157-69. doi: 10.1016/0006-3223(91)90170-q.
• Background Janowsky DS, el-Yousef MK, Davis JM, Hubbard B, Sekerke HJ. Cholinergic reversal of manic symptoms. Lancet. 1972 Jun 3;1(7762):1236-7. doi: 10.1016/s0140-6736(72)90956-7. No abstract available.
• Background Janowsky DS. Serendipity strikes again: scopolamine as an antidepressant agent in bipolar depressed patients. Curr Psychiatry Rep. 2011 Dec;13(6):443-5. doi: 10.1007/s11920-011-0239-6.
• Background Kroon JS, Wohlfarth TD, Dieleman J, Sutterland AL, Storosum JG, Denys D, de Haan L, Sturkenboom MC. Incidence rates and risk factors of bipolar disorder in the general population: a population-based cohort study. Bipolar Disord. 2013 May;15(3):306-13. doi: 10.1111/bdi.12058. Epub 2013 Mar 27.
• Background Insel TR, Wang PS. The STAR*D trial: revealing the need for better treatments. Psychiatr Serv. 2009 Nov;60(11):1466-7. doi: 10.1176/ps.2009.60.11.1466.
• Background Khajavi D, Farokhnia M, Modabbernia A, Ashrafi M, Abbasi SH, Tabrizi M, Akhondzadeh S. Oral scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2012 Nov;73(11):1428-33. doi: 10.4088/JCP.12m07706. Epub 2012 Oct 16.
• Background Newhouse PA, Sunderland T, Tariot PN, Weingartner H, Thompson K, Mellow AM, Cohen RM, Murphy DL. The effects of acute scopolamine in geriatric depression. Arch Gen Psychiatry. 1988 Oct;45(10):906-12. doi: 10.1001/archpsyc.1988.01800340028004.
• Background Poland RE, Tondo L, Rubin RT, Trelease RB, Lesser IM. Differential effects of scopolamine on nocturnal cortisol secretion, sleep architecture, and REM latency in normal volunteers: relation to sleep and cortisol abnormalities in depression. Biol Psychiatry. 1989 Feb 15;25(4):403-12. doi: 10.1016/0006-3223(89)90193-5.
• Background Popa D, El Yacoubi M, Vaugeois JM, Hamon M, Adrien J. Homeostatic regulation of sleep in a genetic model of depression in the mouse: effects of muscarinic and 5-HT1A receptor activation. Neuropsychopharmacology. 2006 Aug;31(8):1637-46. doi: 10.1038/sj.npp.1300948. Epub 2005 Nov 9.
• Background Porter AC, Bymaster FP, DeLapp NW, Yamada M, Wess J, Hamilton SE, Nathanson NM, Felder CC. M1 muscarinic receptor signaling in mouse hippocampus and cortex. Brain Res. 2002 Jul 19;944(1-2):82-9. doi: 10.1016/s0006-8993(02)02721-x.
• Background ROWNTREE DW, NEVIN S, WILSON A. The effects of diisopropylfluorophosphonate in schizophrenia and manic depressive psychosis. J Neurol Neurosurg Psychiatry. 1950 Feb;13(1):47-62. doi: 10.1136/jnnp.13.1.47. No abstract available.
• Background Yildiz A, Vieta E, Leucht S, Baldessarini RJ. Efficacy of antimanic treatments: meta-analysis of randomized, controlled trials. Neuropsychopharmacology. 2011 Jan;36(2):375-89. doi: 10.1038/npp.2010.192. Epub 2010 Oct 27.
• Miravalles C, Kane R, Rossier AT, Quirke J, Aguilar Macias DA, Alvarez-Iglesias A, Chukwudi K, McDonald C, Cannon DM, Hallahan B. Antidepressant efficacy and safety of scopolamine in individuals with bipolar disorder (SCOPE-BD): A randomized double-blind placebo-controlled trial. J Affect Disord. 2026 Mar 15;397:120888. doi: 10.1016/j.jad.2025.120888. Epub 2025 Dec 16.
• Miravalles C, Kane R, McMahon E, McDonald C, Cannon DM, Hallahan B. Efficacy and safety of scopolamine compared to placebo in individuals with bipolar disorder who are experiencing a depressive episode (SCOPE-BD): study protocol for a randomised double-blind placebo-controlled trial. Trials. 2022 Apr 23;23(1):339. doi: 10.1186/s13063-022-06270-4.

Drugs

Indications